Hydroxy-group directivity in the nitroso ene reaction: Diastereo- and regioselective amination of chiral allylic alcohols
Hydroxy-group directivity in the nitroso ene reaction: Diastereo- and regioselective amination of chiral allylic alcohols
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DOI：
10.1021/ja001752w
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发表时间：
2000-10-11
影响因子：
15
通讯作者：
Bottke, N
中科院分区：
文献类型：
--
作者：
Adam, W;Bottke, N
单重态氧1和三唑啉二酮（TRZ）2与1，3-烯丙基应变手性底物的烯反应导致高非对映选择性的苏式构型的烯产物，这是羟基方向性的结果。3.如果这种立体控制对等电子的亚硝基亲烯体起作用，那么手性烯丙醇的非对映选择性胺化反应将是一种有吸引力和方便的合成方法;然而，迄今为止，这种烯烃的烯反应似乎还没有被研究过。4这可能是由于亚硝基烯反应中已知的不希望的副反应，其中所得的羟胺烯产物被原位进一步氧化。5为了克服这些缺点，我们最近建立了一种新的亚硝基亲烯体，即对硝基亚硝基苯（ArNO），它提供持久的烯产物。事实上，目前我们证明，对于这种亚硝基芳烃亲烯体，当使用1，3-烯丙基应变的手性烯丙醇时，羟基方向性有效地起作用。以高的非对映选择性和区域选择性以及良好的产率获得了所需的胺化烯产物。在NMR规模上进行了烯反应的产物研究，所有未知产物都从制备运行中分离出来并进行了充分的表征。产物比率和非对映体选择性由1H NMR谱中特征信号的峰面积直接在粗反应混合物上测定。结果总结于表1中。烯丙醇1a与等摩尔量的亚硝基芳烃在非极性d-氯仿中以高（92：8）非对映选择性（条目1）主要转化为苏型构型的羟胺（2S*，3S*）-2a。在d4-甲醇（69：31，条目3）和d 6-DMSO（66：34，条目4）中，观察到显著较低的非对映选择性。显然，1，3-烯丙基应变基板和亚硝基芳烃亲烯体之间的氢键是负责显着的苏式选择性。在质子甲醇和极性DMSO中，底物/亲烯体氢键通过与溶剂的竞争性分子间相互作用而被抑制。此外，通过如酯1b中的乙酰化或如醚1c中的甲基化对羟基进行化学掩蔽，证实底物/亲烯体氢键在表达烯丙基的高苏式非对映选择性中起作用。
The ene reactions of singlet oxygen1 and triazolinedione (TAD) 2 with 1, 3-allylically strained chiral substrates lead to threo-configured ene products in high diastereoselectivities, a consequence of the hydroxy-group directivity. 3 If such stereocontrol were to operate for the isoelectronic nitroso enophile, an attractive and convenient synthetic methodology would be available for the diastereoselective amination of chiral allylic alcohols; however, the ene reaction of such olefins appears not to have been examined so far. 4 This is presumably due to the undesirable side reactions known for the nitroso ene reaction, in which the resulting hydroxylamine ene products are in situ further oxidized. 5 To circumvent these disadvantages, we recently established a new nitroso enophile, namely p-nitronitrosobenzene (ArNO), which affords persistent ene products. 6 Indeed, presently we demonstrate that for this nitrosoarene enophile the hydroxy-group directivity operates effectively when 1, 3-allylically strained chiral allylic alcohols are employed. The desired aminated ene products have been obtained in high diastereoselectivity and regioselectivity, as well as in good yield.The product studies of the ene reactions were conducted on the NMR scale, all unknown products were isolated from preparative runs and fully characterized. The product ratios and diastereoselectivities were determined directly on the crude reaction mixture from the peak areas of characteristic signals in the 1H NMR spectra. The results are summarized in Table 1. The allylic acohol 1a was converted with an equimolar amount of the nitrosoarene in the nonpolar d-chloroform with high (92: 8) diastereoselectivity (entry 1) predominantly to the threo-configured hydroxylamine (2S*, 3S*)-2a. In d4-methanol (69: 31, entry 3) and d6-DMSO (66: 34, entry 4) significantly lower diastereoselectivities were observed. Evidently, hydrogen bonding between the 1, 3-allylically strained substrate and the nitrosoarene enophile is responsible for the pronounced threo selectivity. In the protic methanol and the polar DMSO, the substrate/enophile hydrogen bonding is suppressed through competitive intermolecular interactions with the solvent. Also chemical masking of the hydroxy group either by acetylation as in the ester 1b or methylation as in the ether 1c corraborate that substrate/enophile hydrogen bonding is at work in expressing the high threo diastereoselectivity for the allylic